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Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity

2004; National Academy of Sciences; Volume: 101; Issue: 26 Linguagem: Inglês

10.1073/pnas.0400567101

1091-6490

Hao-Ming Chang, Matthew Paulson, Michelle Holko, Charles M. Rice, Bryan Williams, Isabelle Marié, David E. Levy,

NF-κB Signaling Pathways

Histone deacetylase (HDAC) activity, commonly correlated with transcriptional repression, was essential for transcriptional induction of IFN-stimulated genes (ISG). Inhibition of HDAC function led to global impairment of ISG expression, with little effect on basal expression. HDAC function was not required for signal transducer and activator of transcription tyrosine phosphorylation, nuclear translocation, or assembly on chromatin, but it was needed for full activity of the signal transducer and activator of transcription transactivation domain. HDAC function was also required for gene induction driven by the IFN regulatory factor 3 transcription factor activated by virus infection, and it was essential for establishment of an antiviral response against Flaviviridae, Rhabdoviridae, and Picornaviridae. Requirement for HDAC function in transcriptional activation may represent a general mechanism for rapid stimulation of ISG transcription.